{"id":229046,"date":"2017-01-02T16:28:11","date_gmt":"2017-01-02T18:28:11","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/en\/?p=229046"},"modified":"2017-01-06T17:20:03","modified_gmt":"2017-01-06T19:20:03","slug":"innovation-is-the-cure","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/innovation-is-the-cure\/","title":{"rendered":"Innovation is the cure"},"content":{"rendered":"
\"Company

L\u00e9o Ramos<\/span><\/a> Company directors and researchers in Itapira, from left: Edson Lima, Eduardo Gottardo, Danielle Cavalcante, Kesley de Oliveira, Marcos Alegria, Ney Leite and German WassermannL\u00e9o Ramos<\/span><\/p><\/div>\n

An ointment containing collagen, used in treating wounds and burns, was presented at the 2016 BIO International Convention, an important global trade fair and conference held in the U.S. city of San Francisco in June 2016.\u00a0 Formulated by the pharmaceutical company Crist\u00e1lia, headquartered in Itapira (SP), the drug does not exactly offer anything new in terms of chemical substance or treatment, but it does feature novelty with regard to how it is manufactured.\u00a0 The drug\u2019s active ingredient, an enzyme once produced only in a culture medium that contained animal protein of the Clostridium histolyticum <\/em>bacteria is now being produced at Crist\u00e1lia in a plant medium.\u00a0 \u201cThis ensures that it contains no animal protein contaminants,\u201d explains physician Ogari Pacheco, Chairman of the Board of Directors and founding partner of the company.\u00a0 Another advantage is that its active ingredient that was once imported is now being produced domestically.\u00a0 \u201cCollagenase provides painless treatment and our biotechnology center has managed to develop the active ingredient in the purest, safest form for patients, which opens the door to international markets.\u201d<\/p>\n

\u201cThis was the first biotechnological product made from microorganisms from Brazilian biodiversity. It was approved by the Brazilian Health Surveillance Agency (ANVISA) in April 2016.\u00a0 We received a warm welcome at the BIO Convention and are now planning to market the collagen domestically as well as internationally,\u201d announced chemist Marcos Alegria, biotechnology director for the company, and a former researcher at Alellyx, a biotech firm in the area of sugarcane and oranges, spun off from \u00a0the Xyllela fastidiosa<\/em> Genome Project completed in 2000.\u00a0 \u201cWhile pursuing my PhD at USP from 1999-2004, I also took part in sequencing the genome of the Xanthomonas citri <\/em>bacteria, which causes citrus canker.\u201d<\/p>\n\n\n\n\n\n\n\n\n\n\n
Company<\/strong><\/td>\n<\/tr>\n
Crist\u00e1lia<\/td>\n<\/tr>\n
R&D center<\/strong><\/td>\n<\/tr>\n
Itapira, SP<\/td>\n<\/tr>\n
N\u00ba Of employees<\/strong><\/td>\n<\/tr>\n
3.186 across the business<\/td>\n<\/tr>\n
Principal products<\/strong><\/td>\n<\/tr>\n
Anesthetics, antipsychotic and erectile dysfunction medications as well as medicinal healing products and burn treatments<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Crist\u00e1lia is hoping its bold move with regard to collagenase will turn it into a representative of the Brazilian pharmaceutical industry that not only makes generic and herbal medicines, but also innovates by marketing process technologies and unique active ingredients.\u00a0 The path to innovation began in 2007 when after seven years of research, the company developed the first Brazilian drug formulated from a novel active ingredient that had passed through all levels of clinical trials and production to arrive at the drug Helleva, then one of only four medications in the world used to treat erectile dysfunction.<\/p>\n

Pacheco, a surgeon, says that the company has always embraced innovation. In 1972, as a partner in a psychiatric clinic known as Crist\u00e1lia, in Itapira, Pacheco saw the potential in a city that had several clinics of this type.\u00a0 He built up Crist\u00e1lia to produce medications for the clinics and went on to produce products that were basically for hospital use such as anesthetics.\u00a0 According to company information, Crist\u00e1lia is present in 95% of Brazilian hospitals and exports to 30 countries in Latin America, Africa and the Middle East.\u00a0 Revenue for 2015 was R$1.7 billion with 7% invested in research, development and innovation.\u00a0 \u201cEighteen percent of this revenue comes from medications developed here in Brazil,\u201d Pacheco says.\u00a0 The company has 3,186 employees, including 31 who hold PhDs and 18 who hold master\u2019s degrees and are engaged in research.<\/p>\n

\"Chemical

L\u00e9o Ramos<\/span>Chemical synthesis to produce pharmaceutical inputs at the R&D laboratoryL\u00e9o Ramos<\/span><\/p><\/div>\n

\u201cWe look for products that are more difficult to produce.\u00a0 It\u2019s not just about making copies,\u201d says the company founder.\u00a0 To follow this path, Crist\u00e1lia began to look outwards; seeking ideas from universities and research institutes that it could build upon.\u00a0 In 2004, the company established a scientific council in collaboration with a former medical school colleague of Pacheco, Dr. Regina Scivoletto, a retired professor at the Institute of Biomedical Sciences (ICB) at USP who serves as council chair.\u00a0 \u201cToday there are dozens of universities and institutes presenting the council with results of their research or that of their development partners,\u201d Scivoletto says.\u00a0 The council looks to academia to find ideas for producing medicines. Within the council, researchers from both inside and outside the company introduce projects, which undergo thorough analysis in terms of patents, regulatory requirements and chemical synthesis.\u00a0 The council is multidisciplinary in nature and includes researchers from USP and from the University of Campinas, (Unicamp), the Federal Universities of Rio de Janeiro (UFRJ), Amazonas (UFAM) and S\u00e3o Paulo (Unifesp).\u00a0 Sometimes, at universities, the chemical formulation is very good in terms of satisfying therapeutic requirements and wins council approval, but during laboratory tests at Crist\u00e1lia, it exhibits toxicity.<\/p>\n

Since 2004, the company has developed 89 patents \u00ad\u00ad\u2013 on molecules, new uses of drugs and processes \u00ad\u00ad\u2013 many international in scope.\u00a0 Crist\u00e1lia\u2019s Center for Research, Development and Innovation, opened in 2009, consists of the New Products Department (DNP) and Research and Innovation Department (P&I) that make use of the same laboratory infrastructure.\u00a0 One of the products under development in the P&I area is nanostructured mesoporous silica, an adjuvant that can be used as a means for delivering oral vaccines.\u00a0 Vaccines such as that for hepatitis, now injectable, may in years to come have a version that can be administered through drops, thus reducing application costs.\u00a0 This type of silica began to take shape in studies conducted by physicist M\u00e1rcia Carvalho de Abreu Fantini, at the Crystallography Laboratory of the USP Physics Institute, and Osvaldo Augusto Sant\u2019Anna, researcher at the Immunochemistry Laboratory of the Butantan Institute, who devised the substance for the vaccine to fight Hepatitis B.\u00a0 In 2005, the company and Butantan signed a partnership agreement to develop the vaccine adjuvant.<\/p>\n

\"Analysis

L\u00e9o Ramos<\/span>Analysis of bacterial cultures in the study of new drugsL\u00e9o Ramos<\/span><\/p><\/div>\n

Mesoporous silica also proved to be capable of expanding the population protected by vaccines. Many vaccines do not immunize everyone; sometimes only 90% of people.\u00a0 \u201cThis has been shown to be the case in animals,\u201d says biomedical scientist Danielle Cavalcante, coordinator of Crist\u00e1lia\u2019s Research and Innovation Department.\u00a0 \u201cOur studies are showing that this type of silica is a platform that can be used in other products.\u00a0 Particles adhere not only to the surface of the vaccine antigen, but also to the molecules of other drugs,\u201d says Cavalcante.\u00a0 The product is currently undergoing clinical testing.\u00a0 She expects mesoporous silica to enter the market in two years.<\/p>\n

No toxic effects<\/strong>
\nAnother drug developed at Crist\u00e1lia and already available on the market is Novabupi (bupivacain hydrochloride), a local anesthetic.\u00a0 \u201cWe modified the chemical structure of this substance to eliminate the part that causes toxicity, making the injectable medicine more acceptable, with fewer side effects,\u201d explains pharmacologist Edson Lima, director of Crist\u00e1lia\u2019s Pharmochemical Division, which produces 53% of the active ingredients used by the company.\u00a0 Lima is a former professor at the Chemical Institute of the Federal University of Rio de Janeiro (IQ-UFRJ) as well as a former researcher at the Institute of Drug Technology (Farmanguinhos), also in Rio de Janeiro.\u00a0 Molecular modification and rearrangement comprise a product line on which Crist\u00e1lia is increasingly focusing its investment, together with the formulation of new active ingredients.\u00a0 One of the professionals working in this area is physicist Kesley Moraes de Oliveira, in charge of triage and computer simulation of new molecules.\u00a0 She worked on the Helleva project and says that the team has already studied more than 180 molecules, and many more are still under analysis.<\/p>\n

\"Reaction

L\u00e9o Ramos<\/span>Reaction calorimeter in the scale-up laboratoryL\u00e9o Ramos<\/span><\/p><\/div>\n

In order to better position itself for the domestic market, the company also focused on the infrastructure involved in manufacturing inputs.\u00a0 In 2013, it opened a biotechnology center in the same industrial complex situated along the highway that connects Itapira to Lind\u00f3ia.\u00a0 There the company is producing three medicines that are currently undergoing clinical trials: the generic monoclonal antibody trastuzumab for treating breast cancer; the protein etanercept, also generic, for treating arthritis and psoriasis; and somatropin, the human growth hormone produced using recombinant DNA technology based on hormone encoder gene cloning.<\/p>\n

Collagenase is produced in another plant, which works in anaerobic biotechnology.\u00a0 All of these initiatives have benefited from the consulting services of Spartaco Astolfi Filho, now a professor at UFAM, and Josef Ernst Thiemann, two former researchers at Biobras, a Minas Gerais company that developed technology to produce human insulin in the late 1970s. That company was bought out by the Danish firm Novo Nordisk in 2001.\u00a0 The two have also encouraged researchers at Crist\u00e1lia to look to Brazil\u2019s biodiversity for new molecules, including those that could be used to produce new antibiotics.<\/p>\n

\"Crist\u00e1lia<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Crist\u00e1lia paves the way to developing new drugs and processes","protected":false},"author":10,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[1567,169],"tags":[212,243,232],"coauthors":[97],"class_list":["post-229046","post","type-post","status-publish","format-standard","hentry","category-corporate-research-en","category-technology","tag-biotechnology","tag-innovation","tag-pharmacology"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/229046","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/10"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=229046"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/229046\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=229046"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=229046"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=229046"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=229046"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}